Our understanding of the molecular control of neuronal function and synaptic transmission is limited because studies are performed using high resolution molecular genetic approaches within the limits of diffraction limited optical microscopy. To increase the understanding of CNS function, it is essential that we can visualize the action of microdomains of molecules or even single molecules in living systems. Near-Field Scanning Optical Microscopy (NSOM) has revolutionized optical microscopy in the physical sciences by permitting investigations of single molecules with visible wavelengths of light. Recently, the applicant's collaborator, Dr. Haydon, has made modifications to such instrumentation and has demonstrated its utility in biological studies of living systems. The goal of this Phase I proposal is to determine the feasibility of developing turn-key instrumentation for sub- diffraction resolution of living cells. They will develop and evaluate an automated photon feedback (PDF) instrument that was recently invented at Iowa State University, to achieve sub-diffraction optical resolution for studies of living cells. The longer term objective (Phases I and II) is to develop an integrated near-field confocal microscope for biological applications.